USE OF REACTION CALORIMETRY TO MONITOR AND CONTROL MICROBIAL CULTURESPRODUCING INDUSTRIALLY RELEVANT SECONDARY METABOLITES

In this article, bench-scale heat flux calorimetry is applied to monit or complex microbial systems producing secondary metabolites and havin g a theologically complex behavior. With such systems, biological meta bolic activity can only be measured accurately if calorimetry is impro ved by on-line correction for stirring power variations using torque m easurement. First, a successful application to the production of the a ntibiotic erythromycin by Saccharopolyspora erythraea is presented. Du ring a batch-culture study, it was shown that heat-flux calorimetry ca n indicate the two main phases of the process, the exact moment of any substrate depletion, and the nature of the depleted substrate. A fed- batch strategy was set up to optimize erythromycin production. Culture s controlled by calorimetry with pulsed addition of the N-source durin g the trophophase and of the C-source during the idiophase allowed a h igher productivity to be reached. Second, an application of heat-flux calorimetry to the production of a bioinsecticide by the sporulating b acterium Bacillus sphaericus is presented. This project aims to unders tand, model and control the factors that effect growth, sporulation an d insecticide production in a chemically defined medium. A batch-cultu re study has shown that calorimetry can be used to monitor the differe nt phases of the process (growth, sporulation) and the different subst rate depletions. The use of a control strategy to optimize production of the insecticidal protein is now under investigation. (C) 1998 Elsev ier Science B.V.